Sains Malaysiana 47(12)(2018): 2941–2950
http://dx.doi.org/10.17576/jsm-2018-4712-02
Identification of Sequence Motifs for the
Protein Components of Type IX Secretion System
(Pengenalpastian Motif Jujukan bagi Komponen
Protein Sistem Perembesan Jenis IX)
REEKI EMRIZAL
& NOR AZLAN NOR MUHAMMAD*
Centre for
Bioinformatics Research, Institute of Systems Biology (INBIOSIS),
Universiti Kebangsaan Malaysia, 43600 UKM Bangi, Selangor Darul Ehsan, Malaysia
Received: 30 May 2018/Accepted: 14 September 2018
ABSTRACT
Porphyromonas gingivalis is the
bacterium responsible for chronic periodontitis, a severe periodontal disease.
Virulence factors produced by this bacterium are secreted by the Type IX
Secretion System (T9SS). The specific functions for each protein component of
the T9SS have yet to be characterized thus limiting our understanding of the
mechanisms associated with the translocation and modification processes of the
T9SS. This study aims to identify the sequence motifs for each T9SS component and
predict the functions associated with each discovered motif using motif
comparisons. We extracted the sequences of 20 T9SS components from the P.
gingivalis proteome that were experimentally identified to be important for
T9SS function and used them for homology searching against fully sequenced
bacterial proteomes. We developed a rigorous pipeline for the identification of
seed sequences for each protein family of T9SS components. We verified that
each selected seed sequence are true members of the protein family hence
sharing conserved sequence motifs using profile Hidden Markov Models. The
motifs for each T9SS component are identified and compared to motifs in the
Pfam database. The discovered motifs for 11 components with known functions
matched the motifs associated with the reported functions. We also suggested
the putative functions for four components. PorM and PorW might form the
putative energy transduction complex. PorP and PorT might be the putative
O-deacylases. The identified motifs for five components matched the motifs
associated with functions that related/unrelated to the T9SS.
Keywords: Motifs; periodontal
disease; type IX secretion System (T9SS)
ABSTRAK
Porphyromonas gingivalis ialah bakteria
yang menyebabkan periodontitis kronik, sejenis penyakit periodontium
yang parah. Faktor kevirulenan yang dihasilkan oleh bakteria ini
dirembeskan oleh Sistem Perembesan Jenis IX (T9SS). Fungsi khusus
bagi setiap komponen protein T9SS masih belum dicirikan menyebabkan
pemahaman mengenai proses translokasi dan pengubahsuaian protein
oleh T9SS adalah terhad. Kajian ini bertujuan untuk mengenal pasti
motif untuk setiap komponen dan meramal fungsi yang boleh dikaitkan
dengan motif tersebut menggunakan kaedah perbandingan motif. Jujukan
untuk 20 komponen penting T9SS yang dikenal pasti melalui uji kaji
diperoleh daripada proteom P. gingivalis. Ia digunakan untuk
pencarian homologi terhadap proteom bakteria yang mempunyai jujukan
genom yang lengkap. Proses analisis yang rapi telah dihasilkan untuk
pengenalpastian jujukan benih bagi setiap famili protein komponen
T9SS. Jujukan benih yang dipilih disahkan sebagai ahli sebenar famili
protein tersebut justeru berkongsi motif terpelihara menggunakan
profil Hidden Markov Models. Motif untuk setiap komponen telah dikenal
pasti dan dibandingkan dengan motif daripada pangkalan data Pfam.
Motif untuk 11 komponen yang telah diketahui fungsinya dipadankan
dengan motif yang dikaitkan dengan fungsi tersebut. Kami turut mencadangkan
fungsi putatif untuk empat komponen. PorM dan PorW berkemungkinan
membentuk kompleks transduksi tenaga. PorP dan PorT berkemungkinan
merupakan O-deasilase. Motif yang dikenal pasti untuk lima komponen
padan dengan motif yang dikaitkan dengan fungsi berkaitan/tidak
berkaitan dengan T9SS.
Kata
kunci: Motif; penyakit periodontium; sistem perembesan jenis IX (T9SS)
REFERENCES
Abby, S.S.,
Cury, J., Guglielmini, J., Néron, B., Touchon, M. & Rocha, E.P. 2016.
Identification of protein secretion systems in bacterial genomes. Scientific
Reports 6: 23080.
Altschul,
S.F., Gish, W., Miller, W., Myers, E.W. & Lipman, D.J. 1990. Basic local
alignment search tool. Journal of Molecular Biology 215(3): 403-410.
Atmakuri,
K., Cascales, E. & Christie, P.J. 2004. Energetic components VirD4, VirB11
and VirB4 mediate early DNA transfer reactions required for bacterial type IV
secretion. Molecular Microbiology 54(5): 1199-1211.
Bailey, T.L.
& Elkan, C. 1994. Fitting a mixture model by expectation maximization to
discover motifs in bipolymers. Proceedings of the Second International
Conference on Intelligent Systems for Molecular Biology 2: 28-36.
Chen, Y.Y.,
Peng, B., Yang, Q., Glew, M.D., Veith, P.D., Cross, K.J. & Goldie, K.N.
2011. The outer membrane protein LptO is essential for the O-deacylation of LPS
and the co-ordinated secretion and attachment of A-LPS and CTD proteins in Porphyromonas
gingivalis. Molecular Microbiology 79(5): 1380-1401.
Das, A.K.,
Cohen, P.T. & Barford, D. 1998. The structure of the tetratricopeptide
repeats of protein phosphatase 5: Implications for TPR-mediated protein-protein
interactions. The EMBO Journal 17(5): 1192-1199.
Dou, Y.,
Osbourne, D., McKenzie, R. & Fletcher, H.M. 2010. Involvement of
extracytoplasmic function sigma factors in virulence regulation in Porphyromonas
gingivalis W83. FEMS Microbiology Letters 312(1): 24-32.
Eddy, S.R.
1995. Multiple alignment using hidden Markov models. Proceedings of the
International Conference on Intelligent Systems for Molecular Biology 3:
114-120.
Escobar,
G.F., Abdalla, D.R., Beghini, M., Gotti, V.B., Rodrigues, V.J., Napimoga, M.H.
& Ribeiro, B.M. 2018. Levels of pro and anti-inflammatory citokynes and
C-reactive protein in patients with chronic periodontitis submitted to
nonsurgical periodontal treatment. Asian Pacific Journal of Cancer
Prevention 19(7): 1927-1933.
Fu, L., Niu,
B., Zhu, Z., Wu, S. & Li, W. 2012. CD-HIT: Accelerated for clustering the
next-generation sequencing data. Bioinformatics 28(23): 3150-3152.
Glew, M.D.,
Veith, P.D., Chen, D., Gorasia, D.G., Peng, B. & Reynolds, E.C. 2017. PorV
is an outer membrane shuttle protein for the type IX secretion system. Scientific
Reports 7(1): 8790.
Gorasia,
D.G., Veith, P.D., Hanssen, E.G., Glew, M.D., Sato, K., Yukitake, H. &
Nakayama, K. 2016. Structural insights into the PorK and PorN components of the Porphyromonas gingivalis type IX secretion system. PLoS Pathogens 12(8):
e1005820.
Gorasia,
D.G., Veith, P.D., Chen, D., Seers, C.A., Mitchell, H.A., Chen, Y.Y. &
Glew, M.D. 2015. Porphyromonas gingivalis type IX secretion substrates
are cleaved and modified by a sortase-like mechanism. PLoS Pathogens 11(9):
e1005152.
Gupta, S.,
Stamatoyannopoulos, J.A., Bailey, T.L. & Noble, W.S. 2007. Quantifying
similarity between motifs. Genome Biology 8(2): R24.
Haffajee, A.D., Cugini, M.A.,
Dibart, S., Smith, C., Kent Jr., R.L. & Socransky, S.S. 1997. The effect of
SRP on the clinical and microbiological parameters of periodontal diseases. Journal
of Clinical Periodontology 24(5): 324-334.
Heath, J.E.,
Seers, C.A., Veith, P.D., Butler, C.A., Muhammad, N.A.N., Chen, Y.Y. &
Slakeski, N. 2016. PG1058 is a novel multidomain protein component of the
bacterial type IX secretion system. PLoS ONE 11(10): e0164313.
Hester, G.,
Kaku, H., Goldstein, I.J. & Wright, C.S. 1995. Structure of mannose-specific
snowdrop (Galanthus nivalis) lectin is representative of a new plant
lectin family. Nature Structural Biology 2(6): 472-479.
Holde, G.E.,
Oscarson, N., Trovik, T.A., Tillberg, A. & Jönsson, B. 2017. Periodontitis
prevalence and severity in adults: A cross-sectional study in Norwegian
circumpolar communities. Journal of Periodontology 88(10): 1012-1022.
Kadowaki,
T., Yukitake, H., Naito, M., Sato, K., Kikuchi, Y., Kondo, Y. & Shoji, M.
2016. A two-component system regulates gene expression of the type IX secretion
component proteins via an ECF sigma factor. Scientific Reports 6: 23288.
Karplus, K.,
Barrett, C. & Hughey, R. 1998. Hidden Markov models for detecting remote
protein homologies. Bioinformatics 14(10): 846-856.
Kopec, K.O.
& Lupas, A.N. 2013. β-Propeller blades as ancestral peptides in
protein evolution. PLoS ONE 8(10): e77074.
Lasica,
A.M., Goulas, T., Mizgalska, D., Zhou, X., De Diego, I., Ksiazek, M. &
Madej, M. 2016. Structural and functional probing of PorZ, an essential
bacterial surface component of the type-IX secretion system of human
oral-microbiomic Porphyromonas gingivalis. Scientific Reports 6:
37708.
Leahy, D.J.,
Aukhil, I. & Erickson, H.P. 1996. 2.0 Å crystal structure of a four-domain
segment of human fibronectin encompassing the RGD loop and synergy region. Cell 84(1): 155-164.
Leone, P.,
Roche, J., Vincent, M.S., Tran, Q.H., Desmyter, A., Cascales, E. &
Kellenberger, C. 2018. Type IX secretion system PorM and gliding machinery GldM
form arches spanning the periplasmic space. Nature Communications 9(1):
429.
Letoffe, S.,
Ghigo, J.M. & Wandersman, C. 1994. Secretion of the Serratia marcescens
HasA protein by an ABC Transporter. Journal of Bacteriology 176(17):
5372-5377.
Nguyen,
K.A., Zylicz, J., Szczesny, P., Sroka, A., Hunter, N. & Potempa, J. 2009.
Verification of a topology model of PorT as an integral outer-membrane protein
in Porphyromonas gingivalis. Microbiology 155(2): 328-337.
Notredame,
C., Higgins, D.G. & Heringa, J. 2000. T-Coffee: A novel method for fast and
accurate multiple sequence alignment. Journal of Molecular Biology 302(1):
205-217.
Ponting,
C.P. & Aravind, L. 1997. PAS: A multifunctional domain family comes to
light. Current Biology 7(11): R674-R677.
Rice, P.,
Longden, I. & Bleasby, A. 2000. EMBOSS: The European Molecular Biology Open
Software Suite. Trends in Genetics 16(6): 276-277.
Roberts,
P.J. & Belsham, G.J. 1995. Identification of critical amino acids within
the foot-and-mouth disease virus leader protein, a cysteine protease. Virology 213(1): 140-146.
Saiki, K.
& Konishi, K. 2010a. The role of Sov protein in the secretion of gingipain
protease virulence factors of Porphyromonas gingivalis. FEMS
Microbiology Letters 302(2): 166-174.
Saiki, K.
& Konishi, K. 2010b. Identification of a novel Porphyromonas gingivalis outer
membrane protein, PG534, required for the production of active gingipains. FEMS
Microbiology Letters 310(2): 168-174.
Sato, K.,
Naito, M., Yukitake, H., Hirakawa, H., Shoji, M., McBride, M.J. & Rhodes,
R.G. 2010. A protein secretion system linked to bacteroidete gliding motility
and pathogenesis. Proceedings of the National Academy of Sciences of the USA 107(1): 276-281.
Shoji, M.,
Sato, K., Yukitake, H., Kamaguchi, A., Sasaki, Y., Naito, M. & Nakayama, K.
2018. Identification of genes encoding glycosyltransferases involved in
lipopolysaccharide synthesis in Porphyromonas gingivalis. Molecular
Oral Microbiology 33(1): 68-80.
Shoji, M.,
Sato, K., Yukitake, H., Naito, M. & Nakayama, K. 2014. Involvement of the
Wbp pathway in the biosynthesis of Porphyromonas gingivalis lipopolysaccharide
with anionic polysaccharide. Scientific Reports 4: 5056.
Shoji, M.,
Ratnayake, D.B., Shi, Y., Kadowaki, T., Yamamoto, K., Yoshimura, F. &
Akamine, A. 2002. Construction and characterization of a nonpigmented mutant of Porphyromonas gingivalis: Cell surface polysaccharide as an anchorage
for gingipains. Microbiology 148(4): 1183-1191.
Skewes-Cox,
P., Sharpton, T.J., Pollard, K.S. & DeRisi, J.L. 2014. Profile Hidden
Markov Models for the detection of viruses within metagenomic sequence data. PLoS
ONE 9(8): e105067.
Sklar, J.G.,
Wu, T., Kahne, D. & Silhavy, T.J. 2007. Defining the roles of the
periplasmic chaperones SurA, Skp, and DegP in Escherichia coli. Genes
and Development 21(19): 2473-2484.
Sonnhammer,
E.L., Eddy, S.R. & Durbin, R. 1997. Pfam: A comprehensive database of
protein domain families based on seed alignments. Proteins: Structure,
Function and Genetics 28(3): 405-420.
Starcevic,
M. & Dell’Angelica, E.C. 2004. Identification of Snapin and three novel
proteins (BLOS1, BLOS2 and BLOS3/reduced pigmentation) as subunits of
biogenesis of Lysosome-related Organelles Complex-1 (BLOC-1). Journal of
Biological Chemistry 279(27): 28393-28401.
Taguchi, Y.,
Sato, K., Yukitake, H., Inoue, T., Nakayama, M., Naito, M. & Kondo, Y.
2016. Involvement of an Skp-Like protein, PGN_0300, in the type IX secretion
system of Porphyromonas gingivalis. Infection and Immunity 84(1):
230-240.
Tonetti, M.S.,
D'Aiuto, F., Nibali, L., Donald, A., Storry, C., Parkar, M. &
Suvan, J. 2007. Treatment of periodontitis and endothelial function.
The New England Journal of Medicine 356(9): 911-920.
Vincent,
M.S., Canestrari, M.J., Leone, P., Stathopoulos, J., Ize, B., Zoued, A. &
Cambillau, C. 2017. Characterization of the Porphyromonas gingivalis type
IX secretion trans-envelope PorKLMNP core complex. Journal of Biological
Chemistry 292(8): 3252-3261.
Vincent,
M.S., Durand, E. & Cascales, E. 2016. The PorX response regulator of the Porphyromonas
gingivalis PorXY two-component system does not directly regulate the type
IX secretion genes but binds the PorL subunit. Frontiers in Cellular and
Infection Microbiology 6: 96.
*Corresponding
author; email: norazlannm@ukm.edu.my
|